Asthma, bronchitis and emphysema are known as Chronic Obstructive Pulmonary Diseases (COPD). COPD is characterized as generalized airways obstruction, particularly of small airways, associated with varying degrees of symptoms of chronic bronchitis, asthma, and emphysema. The term COPD was introduced because these conditions often coexist, and it may be difficult in an individual case to decide which is the major condition producing the obstruction. Airways obstruction is defined as an increased resistance to airflow during forced expiration. It may result from narrowing or obliteration of airways secondary to intrinsic airways disease, from excessive collapse of airways during a forced expiration secondary to pulmonary emphysema, from bronchospasm as in asthma, or may be due to a combination of these factors. Although obstruction of large airways may occur in all these disorders, particularly in asthma, patients with severe COPD characteristically have major abnormalities in their small airways, namely those less than 2 mm internal diameter, and much of their airways obstruction is situated in this zone. The airways obstruction is irreversible except for that which can be ascribed to asthma.
Asthma is a reversible obstructive pulmonary disorder (ROPD) characterized by increased responsiveness of the airway, resulting in airway obstruction. Airway obstruction is defined as an increased resistance to air flow during forced expiration. In asthma, airway obstruction typically results from bronchospasm. The underlying mechanisms causing asthma are unknown, but inherited or acquired imbalance of adrenergic and cholinergic control of airway diameter has been implicated. Asthmatics manifesting such imbalance have hyperactive bronchi and, even without symptoms, bronchoconstriction may be present. Overt asthma attacks may occur when such individuals are subjected to various stresses, such as viral respiratory infection, exercise, emotional upset, nonspecific factors (e.g., changes in barometric pressure or temperature), inhalation of cold air or irritants (e.g., gasoline fumes, fresh paint and noxious odors, or cigarette smoke), exposure to specific allergens, and ingestion of aspirin or sulfites in sensitive individuals. Those whose asthma is precipitated by allergens (most commonly airborne pollens and molds, house dust, animal danders) and whose symptoms are IgE-mediated are said to have allergic or "extrinsic" asthma. They account for about 10 to 20% of adult asthmatics; in another 30 to 50%, symptomatic episodes seem to be triggered by non-allergenic factors (e.g., infection, irritants, emotional factors), and these patients are said to have non-allergic or "intrinsic" asthma. In many persons, both allergenic and non-allergenic factors are significant.
Oxybutynin is used therapeutically in the treatment of intestinal hypermotility and in the treatment of urinary incontinence due to detrusor instability. Oxybutynin is sold for this purpose under the trade name of Ditropan.RTM.. Chemical names for oxybutynin are 4-(diethylamino)-2-butynyl-.alpha.-cyclohexyl-.alpha.-hydroxy benzeneacetate, and 4-(diethylamino)-2-butynylphenylcyclohexyl-glycolate. It is a racemic mixture of the R-enantiomer, R-oxybutynin, and the S-enantiomer, S-oxybutynin.
Use of the S-enantiomer of oxybutynin, S-oxybutynin, for the treatment of urinary incontinence has been described in U.S. Pat. No. 5,532,278, and 5,736,577. The structure of S-oxybutynin (Registry Number 119618-22-3) is shown in formula I. S-oxybutynin is not commercially available at the present time. ##STR1##
Administration of racemic oxybutynin may result in a number of adverse effects. These adverse effects include, but are not limited to, xerostomia, mydriasis, drowsiness, nausea, constipation, palpitations and tachycardia. The amelioration of cardiovascular side effects of racemic oxybutynin, such as tachycardia and palpitations, is of particular therapeutic value.
There is a continuing need for treatments for asthma, particularly those that minimize side effects.